Funding is requested for replacing the console of a high-resolution 600 MHz NMR spectrometer at Northwestern University's Biological NMR Center, a unique resource providing structural and chemical biologists access to high-field instrumentation within a single facility for inter- disciplinary research. Since 1990, with support from NIH and NSF, Northwestern researchers have established and maintained an outstanding resource for macromolecular NMR that has had a significant positive impact on the research programs of multiple investigators both within the college and the university at large. The 600 MHz spectrometer, which is the one and only NMR instrument in the facility, is heavily and continuously used. However, the reliability of this instrument has decreased lately because of a range of problems (including a most persistent FIFO underflow error problem) associated with an aging console, which was last replaced in 1999. The acquisition of a new console along with a replacement compressor (aka cold pack) for the cold probe would cater to the heavy demand for NMR time by a user base that comprises seven well-funded major research groups working on a variety of basic and clinical problems in biology or at the chemistry-biology interface. The research topics being studied include structure-function analyses of transcription factors, structural and functional genomics of infectious agents, electron transfer via protein-protein interactions, structural characterization of natural products, structural biology of kinesin regulation, design and development of novel inhibitors and contrast agents for magnetic resonance imaging and diagnostic applications, and novel synthetic chemistry approaches for medicinal applications. The projects have strong structural and/or functional foci and all of them will benefit from the added sensitivity (mainly from improvements in hardware that have occurred in the past decade), but most significantly, added reliability afforded by a new console and cold probe compressor. The proposed instrument will have all the capabilities to perform any contemporary biomolecular NMR pulse sequence experiment. Since the magnet and cold probe (other than the compressor) have been determined to be in good shape, there are no plans to replace either of them. The new console will have four channels with the first channel for 1H excitation, decoupling and detection, a second channel for excitation, decoupling and broadband detection of biologically-relevant heteronuclei, and a dual channel for excitation and decoupling of biologically-relevant heteronuclei, and pulsed field gradient accessories.